Severe childhood asthma exacerbations: Is treatment response variability in the genes?

Worldwide, asthma is one of the most common causes of medical emergency in children. Failed acute management events comprise a large part of the annual healthcare costs of asthma. These severe exacerbations requiring hospitalization likely also contribute to permanent remodeling and impaired lung function in later life. Various studies have uncovered clinical, environmental, and genetic risk factors for severe asthma and exacerbations that cannot be acutely managed and require hospitalization. Tse and colleagues extend their previous work by adding important new insights into the determinants of failed ED management of pediatric asthma. Using a candidate gene approach and stepwise regression, they identified three SNPs in two candidate genes: IL33, rs7037276, rs1342326 and SPATS2L, rs295137, which when aggregated together significantly increased the odds for ED management failure, with each risk allele increasing failure odds by 83% (95% CI, 36–145%). When these genes markers were combined with validated clinical predictors of acute asthma management failure (viral infection, poor baseline pediatric respiratory assessment measure score, oxygen saturation <92%, fever >38.3°C, and presence of symptoms between episodes) the resulting ability to predict acute management failure was significantly improved (ROC curve=0.82). As discussed in this editorial and the discussion by Tse et al, these novel genetic markers provide new avenues of research for management of acute exacerbations. As the syndrome of asthma continues to be better characterized into multiple endo-phenotypes, we are likely to find that personalized treatment is necessary not only for control of asthma but also for acute rescue of exacerbations.

Duke Scholars

Author Kanecia Obie Zimmerman Pediatrics, Critical Care Medicine

Author Jason Lang Pediatrics, Pulmonary and Sleep Medicine